Evidence presented from this laboratory concerned the detection and partial characterization of a retinoic acid-binding protein (RABP). This protein has an S20 value of 2.0 and an isoelectric pH of 4.6. The ability of various analogs of retinoic acid to bind to this protein correlated with their biological activity. Although no species variability has been observed with respect to tissue distribution of RABP in mice, rats and chick embryo, relatively more of the protein is detected in the tissues of young animals than those of the adult animals. RABP is detected in skin, brain, testis, eye, bladder, prostate, uterus, trachea, and mammary glands of mice and rats. This protein is located in the epithelial cells and not in the connective tissues. Although RABP could not be detected in normal lung and colon, it was present in Lewis lung tumors and in two highly metastatic colon tumors. This protein was below the limits of detection in two weakly metastatic colon tumors. RABP has been detected in the nuclei of chick embryo skin and two experimental tumors. A quantitative method has been developed to measure the binding efficiency of retinoids to RABP. Two cyclopentenyl analogs and trimethylmethoxyphenyl analog of retinoic acid, and 13-cis retinoic acid showed, like retinoic acid, a binding efficiency of 100% for this cellular binding protein.